EPIGENETIC INHERITANCE IN THE MOUSE

Acquired epigenetic modifications, such as DNA methylation or stable c hromatin structures, are not normally thought to be inherited through the germline to future generations in mammals [1,2]. Studies in the mo use have shown that specific manipulations of early embryos, such as n uclear transplantation, can result in altered patterns of gene express ion and induce phenotypic alterations at later stages of development [ 3-5]. These effects are consistent with acquired epigenetic modificati ons that are somatically heritable, such as DNA methylation. Repressio n and DNA methylation of genes encoding major urinary proteins, repres sion of the gene encoding olfactory marker protein, and reduced body w eight can be experimentally induced by nuclear transplantation in earl y embryos M. Strikingly, we now report that these acquired phenotypes are transmitted to most of the offspring of manipulated parent mice. T his is the first demonstration of epigenetic inheritance of specific a lterations of gene expression through the germline, These observations establish a mammalian model for transgenerational effects that are im portant for human health, and also raise the question of the evolution ary importance of epigenetic inheritance. (C) Current Biology Ltd.